Method and device for monitoring acute decompensated heart failure

ABSTRACT

An implantable medical device has an impedance determiner for determining a cardiogenic impedance signal based on electric signals sensed by connected electrodes. A parameter calculator processes the impedance signal to calculate an impedance parameter representative of the cardiogenic impedance in connection with the diastolic phase of a heart cycle. This parameter is then employed by the device for monitoring acute decompensated heart failure status of a subject.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention generally relates to monitoring of acutedecompensated heart failure in subjects having an implantable medicaldevice.

2. Description of the Prior Art

The heart is an essential organ in humans and most animals, pumpingblood throughout the human/animal body. As a consequence, it isfundamentally important that the mechanical pumping properties of theheart operate correctly.

There are several diseases and conditions that negatively affect thesemechanical properties of the heart. A severe such condition is acutedecompensated heart failure (ADHF). This form of heart failure ischaracterized by the sudden inability of the heart to pump efficiently.However it is though not cardiac arrest because the heart does not stopthough the heart pumping action significantly deteriorates.

The inability of the failing heart to pump blood in a forward directioncreates a relative hypovolemic state known as arterial underfilling. Asa response, several neurohormonal factors become activated to maintaineuvolemia by causing fluid retention, vasoconstriction, or both. In thepatient without heart failure, this response terminates once fluidvolume has been restored. However, the activity of these systems remainschronically elevated in the patient with heart failure, thuscontributing to the systemic and pulmonary congestion that are hallmarksof the disorder despite compensatory elevations in endogenous brainnatriuretic peptide (BNP) levels. Neurohormonal activation alsostimulates detrimental activation of pro-inflammatory cytokines andmediators of myocyte apoptosis. As reported in “Acute DecompensatedHeart Failure: A Contemporary Approach to PharmacotherapeuticManagement,” McBride et al, Pharmacotherapy 23(8), pp. 997-1020 (2003),elevations of many of the neurohormones and immunomodulators observed inpatients with ADHF have been associated with a worsening of heartfailure symptoms and a decline in the prognosis of the patients.Although these hormones are elevated in patients with compensated heartfailure, their elevation can precipitate an episode of ADHF if they arenot adequately suppressed by therapy.

Approximately 4.9 million people in the U.S. were diagnosed with ADHF in2003. ADHF is the single most expensive hospital admission diagnosisaccording to the Center for Medicare and Medicaid Administration, withmore than $3.6 billon spent in 1998 alone.

The success in treating ADHF patients and reducing the enormous costassociated with ADHF, is an early patient diagnosis. Today ADHFdiagnosis is mainly limited to patient's history, physical examination,chest X-ray examination and laboratory tests. Characteristic of thisprior art ADHF diagnosis is that it is time-consuming and cumbersome,often requiring dedicated X-ray and imaging facilities in addition toseparate laboratory testing.

SUMMARY OF THE INVENTION

There is therefore a need for time-efficient and simpler ADHF detectionthat can be used in connection with at least a sub-portion of patientshaving a risk of developing ADHF or having a history of previous ADHFlapses. The present invention overcomes these and other drawbacks of theprior art arrangements.

It is a general object of the present invention to provide animplantable medical device having acute decompensated heart failuremonitoring capability.

It is another object of the invention to provide a fast and simple acutedecompensated heart failure detection and diagnosis indication.

Briefly, the present invention involves an implantable medical device(IMD) capable of monitoring acute decompensated heart failure (ADHF)status in a subject for the purpose of detecting an ADHF event ormonitoring relapse from an ADHF event.

The invention is based on the discovery that the impedance associatedwith the subject's heart is fairly similar between healthy subjectstatus and ADHF status during the systolic phase of a heart cycle.However, it was highly surprising that there are significant differencesin the impedance between healthy and ADHF subjects in the diastolicphase of the heart cycle. Thus, by limiting or at least concentratingthe impedance analysis to diastole, a much earlier and more reliableADHF monitoring is obtained as compared to systolic impedance signals ortotal impedance signals over the whole heart cycle.

The IMD therefore has an impedance determiner adapted to determine animpedance signal associated with the subject's heart over at least adiastolic phase of a heart cycle. For this purpose the IMD has or isconnected to at least two electrodes used for applying electric signalsand measuring resulting electric signals to thereby be able to determinethe impedance signal.

A parameter calculator of the IMD is provided for calculating animpedance parameter based on the determined impedance signal. Thiscalculation involves applying a non-zero first weight to the impedancesamples corresponding to diastole and applying a second smaller weightto the impedance samples from systole. In preferred embodiments, thefirst weight is one and the second weight is zero. This basicallyinvolves only utilizing the diastolic impedance samples or a portionthereof in the parameter calculation while omitting the systolicsamples.

A monitor is arranged in the IMD for monitoring the ADHF status of thesubject based on the calculated impedance parameter. This monitoringpreferably involves a comparison of the impedance parameter with areference parameter, where this reference parameter corresponds to apreviously calculated impedance parameter or an average of multiple suchprevious impedance parameters.

An ADHF event or recovery of such an ADHF event is monitored through theparameter comparison. Such ADHF detection can then trigger compensatingtherapies by the IMD and/or generating alert messages urging a contactwith medical personnel.

The present invention also involves a method of monitoring ADHF statususing the diastolic impedance parameter of the present invention.

The invention offers the following advantages:

-   -   Allows ADHF detection and monitoring without the need for        extensive tests and examination at healthcare facilities;    -   Increased specificity and reliability in ADHF monitoring;    -   Provides an early detection of ADHF events; and    -   Can initiate compensating treatment directly upon ADHF        detection.

Other advantages offered by the present invention will be appreciatedupon reading of the below description of the embodiments of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic overview of a patient having an implantablemedical device according to the present invention and an external unitcapable of conducting communication with the implantable medical device.

FIG. 2 is a schematic block diagram of an embodiment of an implantablemedical device according to the present invention.

FIG. 3 is a schematic block diagram of another embodiment of animplantable medical device according to the present invention.

FIG. 4 is a schematic block diagram on an embodiment of the ADHF monitorof FIGS. 2 and 3.

FIG. 5 is a diagram schematically illustrating a difference in impedancesignal from a healthy subject and the subject suffering from ADHF.

FIG. 6 illustrates diagrams of amplitude-normalized impedance signalschanges in three animal subjects from an exacerbation volume overloadprovocation using bipolar impedance measurements between tip and ringelectrode of a right ventricular lead.

FIG. 7 is a diagram of amplitude-normalized impedance signals from humansubjects at different stages of heart failure using quadropolarimpedance measurements by applying a current signal between a tipelectrode of a right ventricular lead and the case and measuring theresulting voltage between a ring electrode of the right ventricular leadand an electrode of a unipolar left ventricular lead.

FIG. 8 is a flow diagram of a method of detecting ADHF according to anembodiment of the present invention.

FIG. 9 is a flow diagram of additional steps of the ADHF detectingmethod in FIG. 8.

FIG. 10 is a flow diagram illustrating an embodiment of the ADHFdetecting step in FIG. 8 according to a particular embodiment.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Throughout the drawings, the same reference characters will be used forcorresponding or similar elements.

The present invention is generally related to monitoring the status ofacute decompensated heart failure (ADHF) in patients, including humanand animal patients, having an implantable medical device (IMD). Thepresent invention teaches an impedance-based ADHF monitoring that allowsfor an early detection of a sudden change in ADHF status, such as adetection of ADHF, and also a more reliable ADHF status monitoring. Thepresent invention achieves this early and reliable monitoring bylimiting or concentrating the analysis of the impedance signal to aselected portion of a heart cycle or beat.

The invention is based on the discovery that changes in ADHF status canbe more accurately followed by analyzing the change in impedance signalassociated the patient's heart during the diastolic phase of the heartcycle. Early indications of ADHF, ADHF relapse and recovery from ADHFare much more clearly evident in the diastolic portion of the impedancesignal as compared to the systolic portion.

This finding was very surprising as the general belief is that heartfailure, possibly with the exception of diastolic heart failure, mainlyaffects the systolic phase of the heart cycle. As a consequence, priorart impedance-based heart failure detection schemes have been using onlythe systolic impedance portion or the impedance signal during the wholeheart cycle.

However, by limiting or concentrating the analysis to the interestingportion of the impedance signal, the present invention will detect evenminor changes in the impedance signal that are due to a change in ADHFstatus. Such minor changes are not detectable in the systolic phase orwould be regarded as baseline variations if the impedance signal duringthe whole heart cycle was instead used. Furthermore, changes in theimpedance signal due to a change in ADHF status first occurs in thediastolic heart cycle phase. It is first when ADHF has been present forsome time that impedance changes become detectable even in the systolicphase. The present invention therefore provides an earlier ADHFdetection by limiting or concentrating the impedance monitoring to thediastole.

The early ADHF detection of the present invention significantly improvesthe chances of successful treatment and recovery from the ADHF conditionas the time of diagnosis strongly affects the outcome of any ADHFtreatment. The invention therefore provides advantages to both IMDpatients and to the society in large by having a possibility of reducingthe hospitalization periods and costs due to the early ADHF detection.

Traditionally, there is a significant risk of sending home patientshaving been treated for ADHF as these patients seem to have fullyrecovered from the ADHF condition. However, several of the patients havethough not stably recovered from the condition and may therefore soonhave to visit a physician due to ADHF relapse. The present invention canbe of advantage also for these patients as the diastolic-based impedanceanalysis of the invention can be used for monitoring the ADHF recoverystatus. As a consequence, premature declaration of fit may be reduced.

FIG. 1 is a schematic overview of a patient 1 having an implantablemedical device, IMD, 100 according to the present invention. In thefigure, the IMD 100 is illustrated as a device that monitors and/orprovides therapy to the heart 10 of the patient 1, such as a pacemaker,cardiac defibrillator or cardioverter. The IMD 100 is, in operation,preferably connected to one or more cardiac leads 200, includingintracardiac leads inserted into a heart chamber (right ventricle in thefigure) and/or endocardial leads.

Though, the IMD 100 preferably has at least one electric lead 200equipped with impedance sensing electrodes, the present invention canalso be used with IMDs 100 not equipped with cardiac leads as long asthe IMD 100 has or is connectable to at least two electrodes used forsensing electric signals for the purpose of calculating an impedancesignal used in the ADHF monitoring of the present invention. In such acase, the IMD 100 could contain at least two electrodes. Alternatively,the IMD 100 comprises at least one electrode, while at least one otherelectrode is positioned on the lead(s) 200. In a further embodiment, allelectrodes are situated in one or more leads 200.

As is well known in the art, impedance measurement can be conductedusing bipolar, tripolar or quadropolar measurements. In the first case,an electric signal (current or voltage signal) is applied using twoelectrodes, which are also employed for sensing the resulting electricsignal (voltage or current signal). In tripolar measurement, theelectric signal is applied using two electrodes, and the resultingelectric signal is sensed over two electrodes of which one was used inthe signal application. Finally, quadropolar measurements use a firstset of two electrodes for signal application and a second set of twodifferent electrodes for signal sensing. The present invention can beused in connection with any of these bipolar, tripolar or quadropolarmeasurements.

Furthermore, the invention can be used in connection with differentimpedance vectors (depends on the particular placement of the applyingand sensing electrodes). The basic feature is that the resultingimpedance signal that is determined based on the applied and sensedsignals contains a contribution from impedance changes from the heart.As a consequence, a preferred impedance signal according to the presentinvention can be the so-called cardiogenic impedance signal, which isgenerally obtained by filtering a raw impedance signal to enhancecardiac frequencies/activities. A typical example could be the usage ofa bandpass filter of 0.32-64 Hz.

FIG. 1 also illustrates an external programmer or clinician'sworkstation 300 that can communicate with the IMD 100. As is well knownin the art, such a programmer 300 can be employed for transmitting IMDprogramming commands causing a reprogramming of different operationparameters and modes of the IMD 100. Furthermore, the IMD 100 can uploaddiagnostic data descriptive of different medical parameters or deviceoperation parameters collected by the IMD 100. Such uploaded data mayoptionally be further processed in the programmer 300 before display toa clinician on a connected display screen 310. In the light of thepresent invention, such diagnostic data can include impedance datameasured by the IMD 100 and/or other diagnostic data relating to ADHFstatus monitoring and detection.

In the present invention, ADHF status is monitored to detect any changesin the ADHF status based on the impedance signal analysis. Theexpression “ADHF status” covers getting AHDF, relapse of ADHF but alsorecovery from ADHF.

FIG. 2 is a schematic block diagram of an IMD 100 according to thepresent invention. The IMD 100 comprises an electrode connectingarrangement 110 arranged in the IMD 100 for providing a connection unitto the at least two electrodes used for the impedance measurements ofthe present invention. In a typical implementation, the connectingarrangement 110 is, in operation, connectable to a proximal end of animplantable electric lead 200 having at least two electrodes inconnection with its opposite distal end, such as a helical/tip electrodeand at least one ring electrode. The lead 200 houses conductors runningthrough the lead body length to provide electrical contact between theelectrode(s) at the distal end with electrode terminals 212 at thedistal end. The connecting arrangement 110 then exhibits matchingterminals 112 that are in electric contact with the electrode terminals212 of the lead 200 to thereby provide an electric connection betweenthe distal electrodes and the IMD 100.

The connecting arrangement 110 can, as has been described above, beconnectable to one or more such implantable electric leads positioned atdifferent anchoring sites in the subject body, such as at differentcardiac positions (different heart chambers and/or intracardial versusendocardial positions).

The present invention is though not limited to lead-carrying electrodes.In clear contrast, one of the electrodes could be the can or case, i.e.housing, of the IMD 100 itself. Furthermore, dedicated electrodes thatare not positioned on cardiogenic leads could also be used and are thenconnected to the arrangement 110.

An input/output (I/O) unit 116 is preferably arranged in the IMD 100 forproviding an interface between the connecting arrangement 110 and theIMD units, in particular an impedance calculator or determiner 120. Thisdeterminer 120 is adapted to determine an impedance signal associatedwith the heart of the subject based on electric signals sensed by theelectrodes connected to the connecting arrangement 110. The impedancesignal reflects the impedance changes of the heart, or at least aportion thereof, such as a heart chamber, during at least a diastolicphase of a heart beat. Thus, the impedance signal can be recorded overmultiple subsequent heart beats, over a single heart beat or over aninterval of a heart beat as long as the interval covers a major portionof the diastolic phase.

A parameter calculator 130 is arranged connected to the impedancedeterminer 120 and is adapted to process and analyze the determinedimpedance signal for the purpose of calculating a diagnostic impedanceparameter. The calculator 130 generates the parameter by applying anon-zero first weight to a diastolic portion of the impedance signalcorresponding to at least a portion of the diastolic phase of the heartbeat and applying a second weight to a non-diastolic (systolic) portionof the impedance signal. The key concept of the invention is that thefirst weight is larger than the second weight.

In a particular embodiment of the present invention, the first weight isone and the second weight is zero. This means that the calculator 130only utilizes the portion of the impedance signal corresponding todiastole for calculating the impedance parameter. Any impedance samplescorresponding to the remaining portion of the heart beat, basicallysystole, are simply ignored or omitted from the calculation. Such anisolated impedance analysis of the impedance signal generates adiastolic impedance parameter representative of the cardiogenicimpedance during the diastolic phase.

Even though a strictly diastolic analysis of the impedance signalprovides a cleaner diastolic impedance parameter, the calculator 130 canalternatively also use one or more impedance samples from the systolicheart cycle phase. However, in such a case, these samples should beweighted lower than corresponding samples from diastole. The impedanceparameter will then concentrate on the diastolic phase even though thereis a (small) contribution from non-diastolic impedance samples.

The present invention can therefore be used in connection withcalculators 130 that are able to identify only those impedance samplesfrom the determiner 120 that corresponds to diastole and calculators 130that use all or at least a majority of the impedance samples from thedeterminer but then applies different weights to the samples to get acomparatively larger contribution from the diastolic impedance samples.

The parameter calculator 130 is preferably connected to a memory 180, inwhich the calculated impedance parameter can be stored for later use.The parameter calculator 130 is also connected to an ADHF monitor 140.The calculator 130 then forwards the calculated impedance parameterdirectly to the monitor 140 or the monitor 140 can fetch it from thememory 180. In either case, the monitor 140 is adapted to monitor theADHF status of the subject based on the impedance parameter. The monitor140 analyzes the received or fetched impedance parameter to detect anysignificant changes in the parameter, which changes are due to changesin the ADHF status of the subject. For instance, the monitor 140 candetect an acute decompensated heart failure event in the subject basedon the parameter analysis. The monitor 140 can also detect such an ADHFrelapse in a subject having a history of ADHF events. However, theimpedance parameter of the invention is not only limited to usage inADHF diagnosis but is also of highly valuable use for monitoringrecovery of a previous ADHF event, which is described further herein.

The ADHF monitor 140 preferably generates a representation of themonitored ADHF status based on the impedance parameter. Thisrepresentation can specify a warning of an emergent ADHF event, containinformation of the ADHF recovery status of an ADHF patient or basicallyspecifying that the ADHF status is normal, i.e. no ADHF event. Therepresentation can also or alternatively contain more detailedinformation, such as information of a difference between a currentlydetermined impedance parameter with a standard or reference parameterrepresenting a healthy subject status. Such a difference can then be arepresentation of an eminent ADHF event, how severe a current ADHF eventis or the ADHF recovery status.

The IMD 100 also comprises a transmitter and receiver 160 with connectedantenna 165. This unit 160 is employed by the IMD 100 for conductingwireless uni- or bidirectional communication with an external unit, suchas the programmer in FIG. 1. The transmitter portion of the unit 160 isin particular suitable for forwarding the impedance parameter from thecalculator 130 or monitor 140 or forwarding the ADHF statusrepresentation from the monitor 140 to the external unit. At theexternal unit a physician can use the parameter or representation fordiagnostic purposes.

A battery 170 is arranged in the IMD 100 for providing the requiredpower supply to the including IMD units.

The units 116, 120, 130, 140, 160 of the IMD 100 can be implemented inhardware, software or a combination of hardware and software.

FIG. 3 is a schematic block diagram of a more detailed implementationembodiment of the IMD 100. The IMD 100 comprises an electric signalapplier 122 connected to the electrodes through the I/O unit 116,terminals 112, 212 and the electric lead 200 in the figure. This signalapplier 122 is arranged for applying a (AC) current or voltage signalthrough two electrodes to at least a portion of the heart. The signalapplication is at least performed during a diastolic phase of a heartbeat but can alternatively be applied over a whole heart cycle ormultiple subsequent cycles.

A signal measurer 124 is likewise connected to two electrodes throughthe I/O unit 116 and the terminals 112, 212 in the connectingarrangement 110. The measurer 124 measures a resulting (AC) voltage orcurrent signal sensed by two electrodes connected to the IMD 100. As wasdiscussed in the foregoing, these two sensing electrodes can be the sameas the electrodes used for signal application (bipolar configuration),one electrode can be common between signal application and sensing(tripolar configuration) or dedicated sensing and application electrodescan be used (quadropolar configuration). The measurer 124 is adapted tomeasure the resulting voltage (or current) signal at least duringdiastole but typically gets voltage (or current) sample through a wholeheart cycle or even multiple heart cycles.

The impedance determiner 120 is connected to the signal applier 122 andmeasurer 124 and calculates the impedance signal based on the appliedcurrent (or voltage) signal and the measured resulting voltage (orcurrent) signal according to known techniques. In a preferredembodiment, the impedance signal is determined as an average signal overmultiple consecutive heart beats, preferably synchronized to each QRS.Such a signal averaging smoothes out temporary deviations that can occurduring a single heart beat for various reasons. In such a case, anaverage of 2 to 20 consecutive heart beats is generally advantageous inthe impedance signal determination.

The parameter calculator 130 can use different techniques foridentifying the interesting portion of the impedance signal from thedeterminer 120, i.e. the portion of the (averaged) impedance signalcorresponding to diastole. In a first embodiment, this interestingdiastolic portion corresponds to the time period following closure ofthe aortic valve up to atrial contraction. If non-zero weights are usedfor both diastolic and non-diastolic impedance signal portions, thelarger first non-zero weight is applied to the impedance samplescorresponding to the above described time period while impedance samplesfalling outside of the time interval are multiplied by the smallersecond weight. Otherwise the impedance samples occurring outside of theinteresting time interval are simply removed from the processing.

The interesting heart cycle portion as defined according to above can bedetermined by a physician and then be programmed into the IMD 100. Thus,the parameter calculator 130 then has access to information, such astime or sample information, allowing identification of the interestingportion from aortic valve closure up to atrial contraction based on sometime or sample reference that is easily identifiable in the impedancesignal, such as the QRS complex.

In another embodiment, the parameter calculator 130 only uses or atleast concentrates the parameter calculation on the impedance signalsamples falling inside the time interval consisting of isometricrelaxation and rapid filling of the ventricles of the heart duringdiastole. This interval can be identified according to techniquessimilar to what is described above.

A signal analyzer 134 can be implemented in the IMD 100 and used by thecalculator 130 for identifying the interesting diastolic part of theimpedance signal. FIG. 5 is a diagram illustrating an example of thechanges in cardiogenic impedance 20, 30 measured over a heart cycle,i.e. including both systole and diastole. With reference to both FIGS. 3and 4, the signal analyzer 134 preferably is configured for identifyinga first local maximum 24, 34 in the impedance signal occurring in thediastolic phase. This identification can be realized by firstidentifying the global maximum 22, 32 in the impedance signal during aheart beat. This global maximum typically corresponds to the transitionfrom systole to diastole. The first local maximum 24, 34 in diastole isthen identified as the first local maximum occurring following theidentified global maximum 22, 32. The signal analyzer 134 can thenutilize well-known techniques for identifying global/local maximums in asignal, which is a straightforward task for the person skilled in theart.

The parameter calculator 130 identifies the interesting portion fromADHF point of view as the portion of the impedance signal correspondingto this peak in the diastole, i.e. from the start of peak to the end ofthe peak or some later time period in diastole.

Test studies have been conducted to and used for determining the onsetof the diastole part of the impedance signal following an identified QRScomplex. As a consequence, the signal analyzer 134 can performprocessing of the impedance signal to identify, for a given heart cycle,such a QRS complex. The diastolic phase is then determined as occurringfollowing a predefined time period, preferably about 300-500 ms, such asabout 400 ms, from the QRS complex up to the end of the diastolic phase,such as the occurrence of the QRS complex in the next heart cycle.

Even though the QRS complex can be identified by the signal analyzer 134from the impedance signal, an electrocardiogram is typically a bettersource for QRS identification. As a consequence, the IMD 100 preferablycomprises an electrocardiogram calculator 136 connected to sensingelectrode(s), preferably attached to implantable cardiac leads 200. Thecalculator 136 then uses the paced or intrinsic electric cardiogenicsignals for determining an electrocardiogram signal. The signal analyzer134 is connected to and receives the electrocardiogram signal from thecalculator 136. The analyzer 134 processes the received signal toidentify the timing of such a QRS complex during a heart cycle. In thisembodiment, the impedance signal and the electrocardiogram signals arepreferably synchronized or time marked using an internal clock (notillustrated). This means that the two signals are recorded in a same ormatching time frame. The parameter calculator 130 identifies relevantperiod of the impedance signal based on the occurrence of the QRScomplex in the electrocardiogram signal. As described above, thisinteresting portion is from about 300-500 ms, such as about 400 msfollowing the timing of the QRS complex up to the end of diastole.

There are several different parameters that the parameter calculator 130could generate and that are suitable for ADHF monitoring purposes. Withreference to FIG. 5, a suitable impedance parameter could berepresentative of a time difference between the occurrence of the globalmaximum 22, 32, i.e. t_(GM), and the first local maximum 24, 34 indiastole, i.e. t_(LM). Another suitable parameter is generated based onthe amplitude of impedance signal in connection with the global maximum22, 32 and the first local maximum 24, 34 in diastole. The parametercould then be a quotient of the impedance values at the two peaks 22,32; 24, 34 or a difference between the impedance values.

Another suitable impedance parameter is a representation of a timedifference between the occurrence of the QRS complex, i.e. t_(QRS), andthe first local maximum 24, 34 in diastole, i.e. t_(LM).

The area under the impedance curve 20, 30 during diastole or oneabove-described interesting portions of diastole is also a suitableimpedance parameter of the invention. The parameter calculator 130 thenperforms an integration calculation according to techniques known in theart to get an estimate of the area under the impedance curve 20, 30 indiastole.

A further example is to perform a line integration of the impedancecurve 20, 30 during diastole. The impedance parameter is thenrepresentative of the length of the impedance curve 20, 30 during thisinteresting phase of the heart cycle. Algorithms for performing lineintegration are well-known in the art.

A further example includes parameters representative of the curvature ofthe first local maximum 24, 34 in diastole.

Thus, there is vast amount of different impedance parameters that can beused according to the present invention and the above-listed ones shouldmerely be seen as preferred but non-limiting examples. The importantfeature is not what particular parameter to use but that the selectedparameter reflects and is representative of the impedance signal duringdiastole. It is anticipated by the present invention that the parametercalculator 130 can calculate more than one impedance parameter perreceived (average) impedance signal. In such a case, the ADHF monitor140 preferably uses these different impedance parameters in the ADHFstatus monitoring.

FIG. 4 is a schematic block diagram of a preferred embodiment of theADHF monitor 140 of FIGS. 2 and 3. The monitor 140 comprises an ADHFdetector 142 that is arranged for detecting ADHF or ADHF relapse orrecurrence in the subject based on the impedance parameter. In apreferred implementation, the detector 142 performs this ADHF detectionbased on a comparison of the determined (average) impedance parameter(s)with at least one reference parameter. This reference parameter can thenbe fetched from the memory 180 illustrated in the IMDs 100 of FIGS. 2and 3.

The reference parameter is of a same parameter type as the determinedimpedance parameter. Thus, if the impedance parameter is indicative ofthe area under the impedance curve during diastole, the referenceparameter is then a corresponding area measure associated with a healthynon-ADHF subject status. This means that if multiple different impedanceparameters are calculated by the parameter calculator 130, the memorypreferably has at least one such reference parameter per parameter type.

The reference parameter can be a standard parameter that is hard codedin the IMD during manufacture or the standard parameter can be receivedby the IMD receiver 160 following implantation into the subject body. Insuch a case, the programmer or some other external communications unitdownloads the standard parameter into the IMD memory 180. Such astandard parameter is then preferably generated based on recordingscollected from a multitude of healthy subjects, i.e. as an average ofthese different recordings. By utilizing impedance measurements duringdiastole from several different healthy IMD subjects, individualvariations in the impedance signal will be smoothed out.

However, the impedance signal is highly dependent on the particularimpedance vector utilized, the positioning of the signal applying andsensing electrodes and also varies from patient to patient. In apreferred embodiment, the reference parameter is therefore based onprevious recording conducted by the IMD 100 on the same patient. Thismeans that a subject-specific impedance parameter comparison is utilizedby the ADHF detector 142, thereby increasing the specificity in the ADHFdetection significantly as compared to standard parameters.

The parameter comparison performed by the ADHF detector 140 ispreferably based on calculating a difference between the impedance andthe reference parameter. If this difference exceeds a defined thresholdparameter, e.g. stored in the memory 180, the detector 142 concludesthat ADHF is detected. Alternatively, a quotient between the impedanceand the reference parameter could alternatively be calculated andcompared to a defined threshold.

If the determined impedance parameter does not significantly deviatefrom the reference parameter, the reference parameter can be updated bya reference updater 132 based on the impedance parameter. Thus, theupdater 132 calculates an updated reference parameter based on theimpedance parameter and the previous reference parameter, such as anaverage or weighted average.

In the case of a significant difference between the reference andimpedance parameters, the ADHF detector may store information of thedifference and/or the impedance parameter in the memory 180. A physiciancan then upload this diagnostic information for medical evaluation.

Furthermore, the ADHF detector 142 in the monitor 140 can be connectedto an ADHF treatment unit 190 provided in the IMD 100 combating adetected ADHF event through application of pacing pulses according to adefined anti-ADHF scheme using the connected cardiogenic leads 200. As aconsequence, ADHF treatment can be initiated directly following itsearly detection according to the invention, thereby significantlyimproving the chances of a fully recovery. In such an embodiment,treatment can be initiated directly once ADHF has been detected by thedetector 142 even though the subject is not present in any healthcarefacility.

The detector 142 can also advantageously generate an alert message,optionally including information of the determined impedance parameteror the difference between it and the reference parameter, upon ADHFdetection. That message can be immediately sent by the transmitter 160to an external unit, whether it is the physician's programmer or aportable IMD-communicating device worn by the subject. Such an alertwill urge the subject to immediately visit a physician unless alreadypresent in a healthcare facility.

In order to provide a reliable confirmation of the presence of ADHF, theimpedance parameter is preferably determined based on the diastoliccardiogenic impedance for several consecutive heart cycles.Alternatively, or in addition, ADHF is confirmed by the detector 142 ifa significant difference exists between the reference parameter andimpedance parameters determined at multiple independent but followingmeasurement instances. Thus, ADHF could be confirmed by the detector 142if there is a significant difference between the impedance and referenceparameter for N following measurement instances, where N is somepredefined integer larger than one.

The IMD 100 of the present invention can also be utilized as a valuabletool when monitoring the recovery from an ADHF event. The ADHF recoverystatus can then be determined by the ADHF monitor 140 based on acomparison of the reference parameter and impedance parameterscalculated from raw impedance data from different time instances. Therecovery can then be followed by monitoring the difference between thereference and impedance parameters, which difference should preferablybe smaller and smaller as the recovery is progressing. A subject canthen be regarded as fully recovered when the difference between thereference parameter and the impedance parameter is insignificant or atleast smaller than a minimum threshold. In order to obtain a reliablerecovery detection, the difference should preferably be insignificant orsmaller than the minimum threshold for at least multiple consecutivemonitoring occasions as discussed above in connection with ADHFdetection.

The IMD 100 preferably performs impedance measurements at multipledifferent time instances. Thus, the current/voltage applier 122 can beconfigured for intermittently or periodically applying, through theconnected electrodes, a current or voltage signal to allow thevoltage/current measurer 124 to measure a resulting voltage/currentsignal for the purpose of determining the impedance signal. Forinstance, the impedance signal can be determined once every hour, oreven more often. However, for most practical implementations it may beenough to measure the cardiogenic impedance one or a limited number oftimes per day, per week or even more seldom.

The units 116, 122, 24, 20, 130, 132, 134, 136, 140, 142, 160 and 190 ofthe IMD 100 can be implemented in hardware, software or a combination ofhardware and software.

FIG. 5 is a diagram schematically illustrating a difference in impedancesignal recorded over a heart cycle for a healthy subject, impedancecurve 24, and at a later occasion where the subject is suffering fromADHF, impedance curve 34. As can be seen from the FIG. 5, there is onlyminor differences in the impedance signals 24, 34 during the systolephase of the heart cycle, while the two curves 24, 24 differssignificantly during diastole. This is the basis for the diastolicimpedance analysis of the present invention.

FIG. 6 illustrates diagrams of amplitude-normalized impedance signalschanges in three canine subjects from an exacerbation volume overloadprovocation using bipolar impedance measurements between tip and ringelectrode of a right ventricular lead. In this study, the animals havebeen exposed to rapid pacing for a couple of weeks. This causes chamberdilation, mechanical dyssynchrony and decreased systolic function. Onceheart failure has been verified, the subjects are exposed to an acutevolume overload provocation where bags of saline solution are infused intheir systems to cause acute fluid congestion. In FIG. 6, the curvebaseline represents the impedance signal before infusion of salinesolution. The curves 1 L, 2 L and 2.5 L are after infusion of one, twoand two and a half liters, respectively. Finally, the curves 2.5 L 1 h,2.5 L 2 h and 3 L 1 h are the impedance signals one or two hours afterinfusion of 2.5 liters or 3 liters.

As can be seen in all experiments, after normalization of the impedancesignal (to get rid of amplitude variations), there are significantmorphological variations in the impedance signal appearing in the samerelative position during the diastolic phase of the heart cycle. Thisvariation occurs about 400 ms after the QRS in the heart cycle.

FIG. 7 is a diagram of amplitude-normalized impedance signals from humansubjects at different stages of heart failure using quadropolarimpedance measurements by applying a current signal between a tipelectrode of a right ventricular lead and the case and measuring theresulting voltage between a ring electrode of the right ventricular leadand an electrode of a unipolar left ventricular lead. FIG. 7 clearlyillustrates that there are only minor differences in the normalizedimpedance signals during systole (corresponds to 0 to up to about 400 msin the diagram). However, there is a significant variation in theimpedance signal in the following diastolic phase.

Taken together these experimental results support the inventive conceptof the invention that variations in impedance signal first and above alloccur in the diastolic phase of the heart cycles. The ADHF monitoringand detection of the present invention is based on this finding bylimiting or at least concentrating the analysis of the impedance signalto this interesting diastolic phase.

FIG. 8 is a flow diagram of a method of monitoring ADHF status in ananimal subject, preferably mammalian subject and more preferably humansubject. The method starts in step S1 that involves determining animpedance signal representative of the impedance associated with thesubject's heart over at least a diastolic phase of a heart beat. Animpedance parameter is calculated in step S2 based on the determinedimpedance signal. This calculation involves applying a non-zero firstweight to a diastolic portion of the impedance signal and applying asecond weight to the non-diastolic portion of the impedance signal. In apreferred embodiment the first weight is one and the second weight iszero. This basically involves only processing the impedance samplesoriginating from diastole while ignoring the other, such as systolic,samples.

A next step S3 monitors the ADHF status in the subject based on thecalculated impedance parameter.

The monitoring method of steps S1 to S3 is preferably performed atmultiple different time instances, such as periodically orintermittently, which is schematically illustrated by the line L1.

FIG. 9 is a flow diagram illustrating additional steps of the monitoringmethod of FIG. 8. Step S10 involves applying a current or voltage signalusing two electrodes to at least a portion of the subject's heart. Twoelectrodes are correspondingly used in step S11 for sensing or capturingthe resulting voltage or current signal. The impedance signal is thendetermined based on the sensed voltage (current) signal and based oninformation of the applied current (voltage) signal in step S1 of FIG.8.

FIG. 10 is a flow diagram illustrating a preferred embodiment of themonitoring step of FIG. 8. The method continues from step S2 in FIG. 8.A next step S20 calculates a difference, preferably the absolute valueof the difference, between the impedance parameter P_(Z) and a referenceparameter P_(R). If this difference is larger than a predefinedthreshold T, the method continues to step S21, where ADHF is diagnosed.In order to increase the reliability in the ADHF detection, ADHF isdiagnosed first when multiple such impedance parameters originating fromdifferent time instances significantly diverge from the referenceparameter.

A next step S22 stores the divergent impedance parameter for laterdiagnostic use by a physician. The optional step S23 triggers uponconfirmed detection of ADHF an anti-ADHF treatment by providingstimulating pulses according to a defined anti-ADHF scheme to thesubject's heart. In addition or alternatively, an ADHF alert message maybe generated and transmitted to a physician or a handheld communicationsterminal of the subject in step S24. The method then continues to stepS1 of FIG. 8.

If ADHF is not present as determined in step S20, the method continuesto step S25, where the optional step S25 updates the reference parameterP_(R) based on the calculated impedance parameter P_(Z) to get anupdated reference parameter P_(R)′. The method continues to step S1 ofFIG. 8.

Although modifications and changes may be suggested by those skilled inthe art, it is the intention of the inventors to embody within thepatent warranted hereon all changes and modifications as reasonably andproperly come within the scope of their contribution to the art.

We claim as our invention:
 1. An implantable medical device comprising:an electrode connecting arrangement connectable to at least twoelectrodes; an impedance determiner that determines an impedance signalassociated with a heart of a subject over at least a diastolic phase ofa heart beat based on electric signals sensed by said at least twoelectrodes; a signal analyzer configured to identify a global maximum insaid impedance signal during said heart beat, and to identify firstlocal maximum in said impedance signal during the diastolic phasefollowing the identified global maximum in the impedance signal; aparameter calculator that calculates, based on said impedance signal, animpedance parameter by applying a non-zero first weight to a diastolicportion of said impedance signal corresponding to a portion of saiddiastolic phase immediately preceding said identified first localmaximum and up to directly following said identified first local maximumand applying a second weight to a non-diastolic portion of saidimpedance signal corresponding to a non-diastolic phase of said heartbeat, said first weight being larger than said second weight; and anacute decompensated heart failure, ADHF, monitor that monitors an ADHFstatus based on said impedance parameter.
 2. The implantable medicaldevice according to claim 1, wherein said electrode connectingarrangement is connectable to at least one implantable electric leadcomprising said at least two electrodes and is attachable to said heart.3. The implantable medical device according to claim 1, wherein saidparameter calculator calculates, based on said impedance signal, adiastolic impedance parameter representative of said impedanceassociated with said heart during at least a portion of said diastolicphase.
 4. The implantable medical device according to claim 1, whereinsaid parameter calculator performs an isolated impedance analysis ofsaid impedance signal during said at least a portion of said diastolicphase to calculate said impedance parameter.
 5. The implantable medicaldevice according to claim 1, wherein said second weight is zero.
 6. Theimplantable medical device according to claim 1, wherein said impedancedeterminer determines said impedance signal as an average of multiplecardiogenic impedances measured during different heart beats.
 7. Theimplantable medical device according to claim 1, further comprising: asignal applier that applies, through said at least two electrodes, acurrent signal or a voltage signal to at least a portion of said heartduring at least said diastolic phase of said heart beat; and a signalmeasurer that measures a resulting voltage signal or a resulting currentsignal sensed by said at least two electrodes over at least a portion ofsaid heart during at least said diastolic phase of said heart beat, saidimpedance determiner calculating said impedance signal based on saidcurrent signal and said resulting voltage signal or said voltage signaland said resulting current signal.
 8. The implantable medical deviceaccording to claim 1, wherein said parameter calculator is calculates,based on said impedance signal, said impedance parameter by applyingsaid non-zero first weight to a diastolic portion of said impedancesignal corresponding to the portion of said diastolic phase followingclosure of the aortic valve up to atrial contraction and applying saidsecond weight to said non-diastolic portion of said impedance signal. 9.The implantable medical device according to claim 1, wherein saidparameter calculator calculates, based on said impedance signal, saidimpedance parameter by applying said non-zero first weight to adiastolic portion of said impedance signal corresponding to the portionof said diastolic phase consisting of isometric relaxation and rapidfilling of the ventricles of said heart and applying said second weightto said non-diastolic portion of said impedance signal.
 10. Theimplantable medical device according to claim 1, wherein said parametercalculator calculates said impedance parameter as representative of atime difference between the occurrence of said global maximum and saidfirst local maximum.
 11. The implantable medical device according toclaim 1, wherein said parameter calculator calculates said impedanceparameter as representative of an amplitude difference between saidglobal maximum and said first local maximum.
 12. The implantable medicaldevice according to claim 1, further comprising: an electrocardiogramcalculator determines an electrocardiogram signal based on electricsignals collected by an electrode of said at least two electrodes; and asignal analyzer that determines, based on said electrocardiogram signal,a timing of a QRS complex during said heart beat.
 13. The implantablemedical device according to claim 1, further comprising a signalanalyzer that determines, based on said impedance signal, a timing of aQRS complex during said heart beat.
 14. The implantable medical deviceaccording to claim 12, wherein said parameter calculator calculates,based on said impedance signal, said impedance parameter by applyingsaid non-zero first weight to a diastolic portion of said impedancesignal corresponding to the portion of said diastolic phase startingabout 400 ms from said timing of said QRS complex and applying saidsecond weight to said non-diastolic portion of said impedance signal.15. The implantable medical device according to claim 1, wherein saidparameter calculator calculates said impedance parameter asrepresentative of an area under an impedance curve obtained from saidimpedance signal, during said at least a portion of said diastolicphase.
 16. The implantable medical device according to claim 1, whereinsaid parameter calculator calculates said impedance parameter asrepresentative of a length of an impedance curve obtained from saidimpedance signal, during said at least a portion of said diastolicphase.
 17. The implantable medical device according to claim 1, whereinsaid ADHF monitor comprises and an ADHF detector that detects ADHF basedon said impedance parameter.
 18. The implantable medical deviceaccording to claim 17, wherein said ADHF detector detects ADHF based ona comparison of said impedance parameter with a reference parameter. 19.The implantable medical device according to claim 18, wherein saidparameter calculator calculates said reference parameter, based on apreviously determined impedance signal, by applying said non-zero firstweight to a diastolic portion of said previously determined impedancesignal corresponding to at least a portion of said diastolic phaseduring a previous heart beat and applying said second weight to anon-diastolic portion of said previously determined impedance signalcorresponding to a non-diastolic phase of said previous heart beat. 20.The implantable medical device according to claim 18, wherein said ADHFdetector compares said impedance parameter with said referenceparameter, and detects ADHF when a difference between said impedanceparameter and said reference parameter exceeds a threshold.
 21. Theimplantable medical device according to claim 20, further comprising aparameter updater that updates said reference parameter when saiddifference between said impedance parameter and said reference parameterdoes not exceed said threshold.
 22. The implantable medical deviceaccording to claim 1, wherein said ADHF monitor monitors a recoverystatus from an ADHF event based on said impedance parameter.
 23. Animplantable medical device as claimed in claim 12 further comprising asignal analyzer that identifies a first local maximum in said impedancesignal in said diastolic phase, and wherein said parameter calculatorcalculates said impedance parameter as representative of a timedifference between occurrence of said QRS complex and said first localmaximum.
 24. An implantable medical device as claimed in claim 13further comprising a signal analyzer that identifies a first localmaximum in said impedance signal in said diastolic phase, and whereinsaid parameter calculator calculates said impedance parameter asrepresentative of a time difference between occurrence of said QRScomplex and said first local maximum.